Patients with an acute coronary syndrome (ACS) and comorbid depression have a 2-fold higher risk for recurrent ACS and mortality, worse quality of life, and higher costs of care than nondepressed ACS patients. The strength of these findings prompted the American Heart Association to recommend routine depression screening for CHD patients. Unfortunately, less evidence is available to guide the treatment of post-ACS depression. Pharmacological and behavioral depression treatments are available, but it has not yet been established that any of them improve event-free survival after ACS. The absence of evidence-based treatment guidelines, coupled with the high prevalence of comorbid depression in ACS, poses a serious dilemma for clinicians. A comparative effectiveness trial is urgently needed to inform clinical practice. We therefore propose a multicenter feasibility/vanguard project comparing the effectiveness of two interventions for post-ACS depression. The project will culminate in a well-designed, well-organized multicenter Phase III clinical trial. The multidisciplinary investigative team includes cardiologists, psychiatrists, clinical health psychologists, statisticians, and clinical trialists. The feasibility project is based on the COPES randomized controlled trial (RCT). COPES tested the acceptability and efficacy of Enhanced Depression Care, a patient preference-driven, stepped care depression intervention for post-ACS patients, to Standard of Depression Care, in which depression screening was followed by physician notification of depression and encouragement to implement a physician-preferred depression treatment. Treatment acceptability was higher in the Enhanced depression care group (54%) than in the Standard of care group (18%). The differential change in depression between groups yielded an effect size of .59, considerably higher than reported for other depression interventions for CHD patients. Although COPES was underpowered to detect effects on major adverse cardiac events (MACE), the incidence of MACE was lower in the Enhanced (4%) than in the Standard depression care arm (13%). The COPES RCT was a small efficacy trial. We are now requesting funds for a multicenter feasibility/vanguard project, so that we can move vigorously towards a Phase III comparative effectiveness trial. Aim 1) To determine the feasibility and effectiveness of the COPES intervention at other sites by conducting a 5-site RCT comparing the COPES intervention to standard care for depression in post-ACS patients, and to obtain estimates of yield, acceptance, and retention for use in planning a large phase 3 clinical trial. Aim 2) To propose a Phase III single-blind, parallel-group, comparative effectiveness RCT for post-ACS patients, testing whether Enhanced depression care results in fewer major adverse cardiovascular events (MACE - recurrent myocardial infarction, hospitalization for unstable angina with documented CHD) and lower all-cause mortality (ACM) across an average 2 year follow-up, compared to Standard of depression care. PUBLIC HEALTH RELEVANCE: Depression and coronary artery disease are projected to be the #1 and #2 worldwide disease burdens by 2020. Not only do each cause disability and death, but depression and CHD co-morbidity appears to add further cost, clinical outcome risk, and diminished quality of life. Yet, we do not have clear evidence about which existing depression treatment algorithm would effectively alleviate both. This CEC grant will accelerate answering this pressing public health issue.